COMMON MEDICAL PRESENTATIONS
Nausea and vomiting
Marcus Harbord
Suzanne Pomfret
Abstract
Nausea and vomiting originate from peripheral (gastrointestinal tract or
middle ear) or central stimuli. Nausea is often precipitated by medication.
Pregnancy, recent surgery and alcohol excess are also common causes.
Rarely, endocrine disease, uraemia and psychiatric causes are contrib-
uting factors. Accurate history and examination usually direct the physi-
cian to the cause and allow a more tailored approach to anti-emetic
therapy if necessary. Antagonists to dopamine, serotonin, or acetylcholine
can all be used. Accurate assessment of fluid status is crucial in vomiting
patients to prevent clinical deterioration and electrolyte disturbance.
Specific investigation and treatment depends on the likely aetiology,
but should be performed urgently if alarm features are present. Relief
of nausea and vomiting is a mainstay of good palliative care.
Keywords anti-emetic; emesis; motility; nausea; vomiting
Nausea is a common symptom and, when accompanied by
vomiting, usually self-limiting. Although there are numerous
causes, originating from peripheral or central stimuli, the history
should identify the cause in the vast majority of cases. This
article provides a structured framework to simplify the
management of nausea and vomiting.
Mechanism of vomiting
Vomiting is a reflex controlled by the ‘vomiting centre’ in the
medulla oblongata. Afferent inputs to this centre originate in
chemo- or mechano-receptors in the upper gastrointestinal tract;
in the chemo-receptor trigger zone (CTZ), which is located
adjacent to the area postrema; or from within the vestibular
system (Figure 1).1 The reflex results in a combination of reverse
peristalsis and relaxation of both pylorus and lower oesophageal
sphincters. The reverse contraction of the pylorus and gastric
antrum leads to expulsion of intestinal contents via the
oesophagus.
Nausea and vomiting can be an appropriate physiological
response to stimuli, such as salmonella infection or neurotrans-
mitter release in motion sickness. Pathological responses repre-
sent disruption to normal pathways, for example within the brain
(e.g. a space-occupying or demyelinating lesion), within the
Marcus Harbord BSc MBBS PhD FRCP is Honorary Senior Lecturer at
Imperial College, London, UK, and Consultant Physician and Gastro-
enterologist at the Chelsea and Westminster Hospital, London, UK.
Competing interests: none declared.
Suzanne Pomfret BA MBBS MRCP is a Speciality Registrar at Chelsea and
Westminster Hospital, London, UK. Competing interests: none declared.
MEDICINE 41:2
autonomic nervous system (e.g. diabetic neuropathy), or within
smooth muscle of the intestine (e.g. amyloid).
Alarm symptoms
There are several red flag symptoms that should alert the clinician to
possible serious organic pathology. For example, anaemia or hae-
matemesis occur in patients with foregut malignancy and significant
weight loss (defined as >5% unintentional weight loss) is present in
a wide range of conditions. Dysphagia must be investigated urgently
to exclude oesophageal malignancy. Nausea is a common symptom
in patients with functional gastrointestinal (GI) disease (e.g. irritable
bowel syndrome) but vomiting must alert the clinician to seek an
alternative diagnosis. Generally, alarm features predicate urgent
gastroscopy with or without cross-sectional imaging.
Aetiology
Nausea and vomiting usually result from problems within the
central nervous system, middle ear or gastrointestinal tract.
Pregnancy, postoperative nausea/vomiting and alcohol excess
are other common causes. Rarer causes comprise endocrine
diseases, uraemia and psychiatric illness. This can best be
remembered by the rule of threes (three main systems, three
other common causes, three rarer causes) (Figure 2).
Often the history and examination provide a clue to the
diagnosis.
 Medication e the more medication a patient takes, the
more likely this is the cause. Consider drug interactions,
especially inducers or inhibitors of cytochrome P450, or
excessive dosing in the context of renal/hepatic disease.
 Chemotherapy-induced nausea and vomiting.
 Postoperative nausea and vomiting are common.
 Toxins e either exogenous (e.g. alcohol, cannabis) or
endogenous (e.g. uraemia).
 Endocrine causes include diabetic ketoacidosis, acute adrenal
insufficiency and hypercalcaemia (usually secondary to
malignancy or primary hyperparathyroidism).
 Gastroparesis is usually idiopathic but can be secondary to
diabetic neuropathy; rarer causes include amyloid neurop-
athy or sarcoidosis.
 Pregnancy is a common cause, especially in the first
trimester. Hyperemesis gravidarum, HELLP syndrome,
pre-eclampsia and acute fatty liver disease of pregnancy
are less common pregnancy-related causes.
 Severe pain (e.g. chest pain suggestive of myocardial
infarction).
 Vestibular neuronitis.
 Cerebellar disease.
 Intracranial bleed.
 Infective gastroenteritis, particularly if friends/family are
ill, when a history of fever or diarrhoea/abdominal
cramping are present. The cause is usually viral.
 Cyclical vomiting describes intermittent episodes of vom-
iting lasting several days, usually separated by periods of
normality lasting a few months. It is more common in
marijuana users2 and patients with diabetes mellitus.
 Constipation, especially in the elderly.
 Intra-abdominal inflammatory causes include appendicitis,
cholecystitis, pancreatitis, inflammatory bowel disease,
87 Ó 2013 Elsevier Ltd. All rights reserved.
 COMMON MEDICAL PRESENTATIONS
Neurological control of the foregut
Coeliac
Superior
mesenteric
Sympathetic control of the foregut arises from the thoracic spinal
cord. The sympathetic chain (green line) connects to the coeliac
and superior mesenteric ganglia via the great and small splanchnic
nerves (thin red arrows). Post-ganglionic fibres (black arrows)
innervate the stomach, small bowel and proximal colon.
Efferent sympathetic nerves inhibit intestinal motility; afferent
nerves transmit nociceptive stimuli.
Parasympathetic stimulation increase gastrointestinal
motility, mediated by the vagus nerve. Afferent nerves
(thick red arrows) synapse in the nucleus tractus
solitarius in the medulla; thereafter fibres travel to the area
postrema in the floor of the fourth ventricle (also known as the
chemo-receptor trigger zone as it is sensitive to humoral factors
such as drugs, neurotransmitters).1 This connects with higher
centres. Vomiting is initiated by efferent vagal nerve fibres.
Figure 1
cholangitis and peritonitis. Episodic right upper quadrant
pain and vomiting suggest gallstone disease.
 Dyspepsia, often caused by Helicobacter pylori or anti-
inflammatory drug use.
 Gastric outlet obstruction.
 Lower gastrointestinal obstruction e faecal vomiting may
be present.
 Bulimia should be considered in patients with dental
erosions, calluses on the dorsum of the hands, salivary
gland hypertrophy or lanugo hair.3
 Rare causes include acute angle glaucoma, high-altitude
sickness and Bouveret’s syndrome (foregut obstruction
due to gallstone impaction).
Investigations
Baseline investigations include full blood count, bone profile,
liver function, and measurement of serum urea and electrolytes,
MEDICINE 41:2
magnesium and (venous) bicarbonate, and plasma glucose.
Capillary blood glucose and a urine dipstix for ketones should be
routine. Patients with significant vomiting often have a hypo-
kalaemic metabolic alkalosis. Vomiting causes loss of hydrogen
ions, raising plasma bicarbonate concentrations. Consequently,
the sodium bicarbonate concentration is high within the col-
lecting ducts. To maintain sodium balance, sodium is reabsorbed
in exchange for potassium, which results in hypokalaemia. Urine
chloride will be low (<25 mmol/litre) due to gastric losses.
A pregnancy test should be performed in women of child-
bearing age. Arterial blood gases should be measured in sick
patients, a septic screen is necessary in febrile patients, and stool
cultures should be obtained if there is co-existent diarrhoea.
A plain abdominal X-ray may demonstrate fluid-filled small
bowel loops indicative of bowel obstruction, and an erect chest
X-ray should be obtained if perforation of the bowel is suspected.
Subsequent investigations depend on the suspected aetiology.
 Peptic ulcer disease requires gastroscopy plus biopsies as
indicated for H. pylori or malignancy. Note that H. pylori
can be detected by stool antigen testing, which can be used
for screening and follow-up.
 Gastric outlet obstruction should be investigated by
gastroscopy, once the stomach has been decompressed
(with a wide-bore nasogastric tube).
 Gallstones can usually be confirmed by an abdominal
ultrasound scan.
 GI malignancy requires an abdominal/pelvic CT scan
together with a gastroscopy or and colonoscopy.
 Pseudo-obstruction requires a water-soluble contrast
follow-through or enema, usually in patients with obstruc-
tion in whom gastroscopy or abdominal CT scan has
demonstrated no lesion, particularly if gas is present within
the rectum. Intestinal dilatation may be present in chronic
intestinal pseudo-obstruction in which nausea and vomiting
are common.4
 Gastroparesis requires scintigraphic gastric emptying
studies.
 ‘Red flag’ symptoms, such as headache, loss of conscious-
ness or seizures, should lead to a low threshold for cerebral
imaging.
 Vestibular neuronitis may require an ENT opinion.
Complications
In addition to the problems directly related to the underlying
pathology, patients with nausea and vomiting are at risk of dehy-
dration and volume depletion as well as significant electrolyte
disturbance; fluid and electrolyte status should be regularly moni-
tored. In addition, aspiration or oesophageal rupture are serious
complications. Haematemesis may occur with MalloryeWeiss tears
of the oesophagus after vomiting. If vomiting is chronic, nutritional
deficiencies may also appear. In the management of nausea and
vomiting these complications should always be considered.
Management
Initial treatment
The mainstay of initial treatment comprises fluid replacement
and anti-emetics (Figure 3). Consequently, it is important to
assess the patient’s volume status. The most sensitive indication
88 Ó 2013 Elsevier Ltd. All rights reserved.
 COMMON MEDICAL PRESENTATIONS

Causes of nausea and vomiting Labyrinthine (H1, Ach)

Rarer causes Motion sickness
Vestibular neuronitis HSV reaction
Anorexia/bulimia
Psychological Tumour
Psychogenic vomiting ′
Meniere’s
↑PTH
↓PTH
Addison’s Endocrine Gastrointestinal
↑Thyroid diseases
DKA
Mechanical
Obstruction Gastroparesis
Pseudo-obstruction
Uraemia Small/large bowel
Causes of nausea H. pylori
and vomiting Ulceration
NSAIDs
Other common causes
Nausea
Pregnancy
Hyperemesis
gravidarum Postoperative Medication, e.g. chemotherapy, digoxin, antbiotics
Alcohol excess Infective gastroenteritis (DA and 5-HT)
High serum corrected calcium
Gallstone disease
Central Cyclical vomiting
Other Pancreatic cancer
Medication Intra-abdominal inflammation
Tumour e.g. pancreatitis
Raised ICP GORD
Migraine (DA)
MS
IBS
Functional
Non-ulcer dyspepsia

HSV, Herpes simplex virus; DA, dopamine; 5-HT, serotonin; H1, histamine; Ach, acetyl choline; NSAIDs, non-steroidal-anti-inflammatory drugs;
GORD, gastro-oesophageal reflux disease; IBS, irritable bowel syndrome; ICP, intracranial pressure; DKA, diabetic keto-acidosis; PTH, parathyroid hormone.

Figure 2

of volume depletion is a postural drop in blood pressure while
standing or sitting. Other features such as skin turgor, degree of
venous filling, presence of postural hypertension, pulse rate and
the degree of thirst are less reliable. Most patients admitted to
hospital with nausea and vomiting will require intravenous fluid
replacement with crystalloid, usually sodium chloride 0.9%
containing potassium chloride, guided by electrolyte status. The
presence of pre-existing co-morbid conditions such as heart,
renal or liver failure should be considered when prescribing
fluids. If aspiration is likely, based on chest X-ray and clinical
examination, antibiotics with anaerobic cover should be
prescribed; co-amoxiclav is adequate in most cases. If an upper
gastrointestinal bleed is suspected, prompt resuscitation and
gastroscopy are indicated (see MEDICINE 2011; 39(2): 94e100).
Anti-emetics
There are five neurotransmitter sites that are used in the phar-
macological management of nausea and vomiting:
 M1 e muscarinic acetylcholine
 D2 e dopamine
 H1 e histamine
 5-HT3 e hydroxytryptamine (serotonin)
 neurokinin-1 (NK-1) receptor e substance P.
The receptors are found mostly in the area postrema, except for
H1 receptors. H1 receptors are present in the vestibular nucleus,
and there is a concentration of 5-HT3 receptors within vagal
afferent neurones. The choice of anti-emetic depends on the
likely cause of the symptoms.5 Different anti-emetics or combi-
nations can be used, especially if the symptoms are persistent or
severe (Table 1).
Specific management points
 Review the patient’s usual medication and consider stop-
ping/substituting those drugs whose introduction coin-
cided temporally with the onset of symptoms.
 Intravenous fluids are often required to replace fluid and
electrolyte losses (including third-space losses into the GI
tract).
 Acid suppression (e.g. omeprazole) often abolishes
nausea/vomiting caused by dyspepsia or non-steroidal
anti-inflammatory drugs (NSAIDs).
 H. pylori, if present, should be eradicated.
 In oncological and palliative patients, reversible factors
such as excess opioid therapy, constipation, electrolyte
abnormalities and raised intracranial pressure should be
sought and corrected. Raised intracranial pressure can be

MEDICINE 41:2 89 Ó 2013 Elsevier Ltd. All rights reserved.

 COMMON MEDICAL PRESENTATIONS

Overview of initial treatment, investigation, alarm features and specific therapies in nausea and vomiting

Initial treatments

Assess volume status

Palliative care
Correct electrolytes Hypokalaemia and
Optimize symptomatic control
metabolic alkalosis
Metoclopramide
Specific treatments Anti-dopaminergic Domperidone
Prochlorperazine
Surgery
Relieve Anti-cholinergic
Stenting (palliative) Anti-emetic
obstruction Anti-histamine
Treat Anti-serotonergic
PPI (Corticosteroids)
inflammation
H. pylori Rx
Nausea NBM/IVI
Cyclical vomiting and vomiting Suspected GI obstruction NGT
Postoperative vomiting Surgical referral
Pregnancy
IBS

Investigation
Alarm features ?Upper GI malignancy Bloods (U&E, LFT, Ca++, PO4––, Mg++, FBC)
Initially
AXR/erect CXR if obstruction
Vomiting
> 5% unintentional weight loss Gastroscopy
Anaemia Ultrasound abdomen
Haematemesis Abdominal CT
Consider
Barium study
(usually if nausea
Brain CT
> 5 weeks/vomiting
ENT option
> 5 days)

PPI, proton pump inhibitor; IBS, irritable bowel syndrome; NBM/IVI, nil by mouth/intravenous infusion; NGT, nasogastric tube; U&E, urea and electrolytes;
LFT, lung function test; Ca++, PO4––, calcium phosphate; Mg++, magnesium; FBC, full blood count; AXR, abdominal X-ray; CXR, chest X-ray; CT, computed tomography;
ENT, ear, nose and throat.

Figure 3

treated with high-dose dexamethasone 8e16 mg twice
daily). In palliative cases gastric secretions can be inhibited
with octreotide, and patients’ comfort enhanced with
sedatives such as midazolam.7
 Erythromycin has a prokinetic rather than anti-nausea
action but its usefulness is limited by a low therapeutic
index.
 In patients presenting with gastrointestinal obstruction:
 keep nil by mouth and insert a nasogastric tube
 seek a surgical opinion
 prefer centrally acting anti-emetics, such as haloperidol,
prochlorperazine, or levomepromazine, as they have
fewer prokinetic effects.
 A 3-week reducing course of prednisolone is more effective
than antiviral therapy in vestibular neuronitis, which is
presumed to be due to a viral infection (specifically herpes
simplex virus reactivation).8 Physical therapy for vestib-
ular rehabilitation may also have a role.
 Pregnancy-related nausea and vomiting requires reassur-
ance and nutritional advice. The obstetric team must
always be informed. In severe cases, metoclopramide and
cyclizine are first-line medication. Regular pyridoxine
has been shown to be effective.9,10 Phenothiazines,
antihistamines, selective 5-HT receptor antagonists and
dopamine agonists are all safe in pregnancy.11 Combina-
tions are often required and corticosteroids may have
a role for patients with hyperemesis resistant to conven-
tional management.12
 Tricyclic antidepressants (e.g. amitriptyline) can be used in
intractable cyclical vomiting syndrome. Drug-resistant
cases can be referred for gastric pacing, using the Enter-
raÔ system (a neuro-stimulator placed in the subcuta-
neous fat, with electrodes implanted into the stomach).
 Postoperative vomiting is common. A large, controlled trial
has demonstrated that dexamethasone 4 mg and/or droper-
idol (antihistaminic, antiserotonergic and antidopaminergic
actions) 1.25 mg at induction, or ondansetron 4 mg towards
the end of surgery, both effectively reduce nausea.12 A recent
meta-analysis of randomized-controlled trials found that
dexamethasone at doses more than 0.1 mg/kg is an effective
adjunct in multimodal strategies to reduce postoperative pain
and opioid consumption after surgery.13
For many patients, nausea and vomiting are self-limiting condi-
tions that are effectively managed by patients themselves. In
cases that require medical attention, assessing illness severity,
determining a likely aetiology and prompt management are

MEDICINE 41:2 90 Ó 2013 Elsevier Ltd. All rights reserved.

 COMMON MEDICAL PRESENTATIONS

Anti-emetic classification
Class Receptor Examples Main uses Important side effects

Anticholinergic M1 Procyclidine, scopolamine Labyrinthine disorders Dry mouth

agents (transdermal)
Antihistamines H1 Cyclizine, promethazine General plus labyrinthine Sedation
disorders
Benzamides D2, weak 5-HT3 Metoclopramide, domperidone General especially migraine Tardive dyskinesia
(poor CNS penetration, no and gastroparesis Domperidone e fewer
parenteral preparation) extra-pyramidal effects
Butyrophenones D2 Haloperidol, Droperidol Postoperative nausea and Sedation, QT prolongation,
vomiting, preanaesthetic hypotension, acute dystonia
sedation
Phenothiazines D2, some M1 Prochlorperazine, Chemotherapy-induced emesis Extra-pyramidal reactions,
and H1 chlorpromazine hypotension
Serotonin receptor 5-HT3 Ondansetron Chemotherapy-induced emesis Mild headache, asthenia,
antagonists constipation
Neurokinin receptor NK-1 Aprepitant (used in conjunction Chemotherapy-induced emesis Hepatic impairment, many
antagonists with dexamethasone and 5-HT3 drug interactions
receptor antagonist6)
Glucocorticoids Dexamethasone Chemotherapy-induced emesis, Multiple
palliative care
Cannabinoids Nabilone Limited use, chemotherapy- Vertigo, xerostomia, hypotension,
induced emesis dysphoria, behavioural effects
Benzodiazepines Lorazepam, diazepam Weak anti-emetics Sedation

Table 1

essential. Lifestyle advice e NSAID avoidance, smoking cessa-
tion and reduction in alcohol intake are an important part of the
overall management plan and should not be forgotten. A nauseous all of the time. nothing was working”. J Am Med Assoc
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MEDICINE 41:2 91 Ó 2013 Elsevier Ltd. All rights reserved.